scholarly journals Gata2-L359V impairs primitive and definitive hematopoiesis and blocks cell differentiation in murine chronic myelogenous leukemia model

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ya-Kai Fu ◽  
Yun Tan ◽  
Bo Wu ◽  
Yu-Ting Dai ◽  
Xiao-Guang Xu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Rna Sequencing ◽  
Early Stage ◽  
Binding Capacity ◽  
Adult Life ◽  
Myelogenous Leukemia ◽  
Mice Model ◽  
Altered Expression ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Primitive Erythropoiesis

AbstractGATA2, a key transcription factor in hematopoiesis, is frequently mutated in hematopoietic malignancies. How the GATA2 mutants contribute to hematopoiesis and malignant transformation remains largely unexplored. Here, we report that Gata2-L359V mutation impeded hematopoietic differentiation in murine embryonic and adult hematopoiesis and blocked murine chronic myeloid leukemia (CML) cell differentiation. We established a Gata2-L359V knockin mouse model in which the homozygous Gata2-L359V mutation caused major defects in primitive erythropoiesis with an accumulation of erythroid precursors and severe anemia, leading to embryonic lethality around E11.5. During adult life, the Gata2-L359V heterozygous mice exhibited a notable decrease in bone marrow (BM) recovery under stress induction with cytotoxic drug 5-fluorouracil. Using RNA sequencing, it was revealed that homozygous Gata2-L359V suppressed genes related to embryonic hematopoiesis in yolk sac, while heterozygous Gata2-L359V dysregulated genes related to cell cycle and proliferation in BM Lin-Sca1+c-kit+ cells. Furthermore, through chromatin immunoprecipitation sequencing and transactivation experiments, we found that this mutation enhanced the DNA-binding capacity and transcriptional activities of Gata2, which was likely associated with the altered expression of some essential genes during embryonic and adult hematopoiesis. In mice model harboring BCR/ABL, single-cell RNA-sequencing demonstrated that Gata2-L359V induced additional gene expression profile abnormalities and partially affected cell differentiation at the early stage of myelomonocytic lineage, evidenced by the increase of granulocyte–monocyte progenitors and monocytosis. Taken together, our study unveiled that Gata2-L359V mutation induces defective hematopoietic development and blocks the differentiation of CML cells.

scholarly journals Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 709-721 ◽  
Author(s):  
HP Koeffler
Keyword(s):  
Cell Differentiation ◽  
Acute Myelogenous Leukemia ◽  
Early Stage ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Therapeutic Implications ◽  
Stage Of Development ◽  
Acute Myelogenous

Abstract A prominent phenotypic abnormality of human acute myelogenous leukemia cells is the inability of the cells to differentiate to functional mature cells; instead, the cells are blocked at an early stage of development and remain in the proliferative pool and rapidly accumulate. Investigation of the induction of myeloid leukemic cell differentiation has made recent advances with the development of several human myelogenous leukemia cell lines. The lines provide models to study the biology of myeloid differentiation and to identify inducers of differentiation of myeloid leukemic blood cells. This review critically examines the inducers of leukemic cell differentiation and their potential therapeutic importance.

scholarly journals Identification of lncRNA, MicroRNA, and mRNA-Associated CeRNA Network of Radiation-Induced Lung Injury in a Mice Model

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989101
Author(s):  
Yida Li ◽  
Liqing Zou ◽  
Xi Yang ◽  
Li Chu ◽  
Jianjiao Ni ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lung Injury ◽  
Early Stage ◽  
Cell Lineage ◽  
Late Complications ◽  
Control Group ◽  
Messenger Rnas ◽  
Mice Model ◽  
Target Mrnas ◽  
Radiation Induced

Radiation-induced lung injury (RILI) can be challenging for thoracic radiotherapy, thus investigating its mechanisms of related pathophysiological process is needed. Long noncoding RNAs (lncRNAs) was found to participate in normal tissue damage induced by ionizing irradiation. Here, we first profiled the dysregulation of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) of RILI in mice model receiving 12 Gy thoracic irradiation. The lung tissue was collected 48 hours after irradiation, after which an RNA library was built by RNA sequencing. Compared with the control group, 461 mRNAs and 401 lncRNAs were significantly upregulated, while 936 mRNAs and 501 lncRNAs were significantly downregulated. Then we predicted target miRNAs of the dysregulated lncRNAs and the target mRNAs of these miRNAs. Next, functional annotations of these target mRNAs were performed. Results showed some pathways apparently dysregulated, such as Th1 and Th2 cell differentiation, Th17 cell differentiation, and hematopoietic cell lineage. Through this study, we also highlighted that T helpers could be vital in RILI through lncRNA-miRNA-mRNA network, therefore causing fibrosis, indicating that RNA dysregulation in early stage of RILI may cause severe late complications. Thus, research on the target mechanism and early intervention of lncRNAs with associated competing endogenous RNA network will benefit the treatment of RILI.

scholarly journals Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 709-721 ◽  
Author(s):  
HP Koeffler
Keyword(s):  
Cell Differentiation ◽  
Acute Myelogenous Leukemia ◽  
Early Stage ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Therapeutic Implications ◽  
Stage Of Development ◽  
Acute Myelogenous

A prominent phenotypic abnormality of human acute myelogenous leukemia cells is the inability of the cells to differentiate to functional mature cells; instead, the cells are blocked at an early stage of development and remain in the proliferative pool and rapidly accumulate. Investigation of the induction of myeloid leukemic cell differentiation has made recent advances with the development of several human myelogenous leukemia cell lines. The lines provide models to study the biology of myeloid differentiation and to identify inducers of differentiation of myeloid leukemic blood cells. This review critically examines the inducers of leukemic cell differentiation and their potential therapeutic importance.

scholarly journals Altered expression of cytochrome P450 and possible correlation with preneo plastic changes in early stage of rat hepatocarcinogenesis

2005 ◽  
Vol 26 (6) ◽  
pp. 737-744 ◽  
Author(s):  
Lin-lin LIU ◽  
Li-kun GONG ◽  
Xin-ming QI ◽  
Yan CAI ◽  
Hui WANG ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Early Stage ◽  
Altered Expression ◽  
Plastic Changes

GAMYB TF modulates bHLH142 and is homeostatically regulated by TDR TF during rice anther tapetal and pollen development

2021 ◽  
Author(s):  
Swee-Suak Ko ◽  
Min-Jeng Li ◽  
Yi-Cheng Ho ◽  
Chun-Ping Yu ◽  
Ting-Ting Yang ◽  
...  
Keyword(s):  
Pollen Development ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Specific Binding ◽  
Biological Functions ◽  
Altered Expression ◽  
Regulatory Pathways ◽  
E Box ◽  
And Function ◽  
Different Tissues

Abstract GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a “hub” in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of bHLH142 promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. The altered expression of TFs highlights the importance that a tight, precise, and coordinated regulation among these TFs is essential for normal pollen development. Most notably, this study illustrates the regulatory pathways of GAMYB and UDT1 that rely on bHLH142 in a direct and an indirect manner, respectively, and function in different tissues with distinct biological functions during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

scholarly journals High Fat Diet Induces Adhesion of Platelets to Endothelium in Two Models of Dyslipidemia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jaime Gonzalez ◽  
Wendy Donoso ◽  
Natalia Díaz ◽  
María Eliana Albornoz ◽  
Ricardo Huilcaman ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Early Stage ◽  
Endothelial Activation ◽  
Mice Model ◽  
High Fat ◽  
Early Stages ◽  
Endothelial Surface ◽  
Two Stages ◽  
Adhesion Of Platelets

Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE−/−mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE−/−mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cellsin vivo. These findings support studying the participation of platelets in the formation of atheromatous plate.

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